CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1

Cancer Cell International

Xin-Ran Chu¹  You Jiang¹  Jun Lu¹  Yong-Ping Zhang¹  Jian Pan²  Yan-Fang Tao²  Jing-Jing Pan²  Shao-Yan Hu²  Shui-Yan Wu³  Juan-Juan Yu⁴  Fang Fang⁴  Yi Xie⁴  Hai-Bo Cao⁴  Hai-Rong Wang⁴  Chen-xi Feng⁴  Gen Li⁴  Jian-Wei Wang⁴  Xiao-Lu Li⁴  Di Wu⁴  Zi-Mu Zhang⁴  Zheng Zhang⁴  Ran Zuo⁴  Xin-Mei Liao⁴  Zhi-Heng Li⁴  Si-Qi Jia⁵  Yan-Ling Chen⁵ 

[1] Department of Hematology, Children’s Hospital of Soochow University, No.92 Zhongnan Street, SIP, 215003, Suzhou, Jiangsu, China;Department of Hematology, Children’s Hospital of Soochow University, No.92 Zhongnan Street, SIP, 215003, Suzhou, Jiangsu, China;Institute of Pediatric Research, Children’s Hospital of Soochow University, No.92 Zhongnan Street, SIP, 215003, Suzhou, China;Department of Hematology, Children’s Hospital of Soochow University, No.92 Zhongnan Street, SIP, 215003, Suzhou, Jiangsu, China;Intensive Care Unit, Children’s Hospital of Soochow University, 215003, Suzhou, China;Institute of Pediatric Research, Children’s Hospital of Soochow University, No.92 Zhongnan Street, SIP, 215003, Suzhou, China;Institute of Pediatric Research, Children’s Hospital of Soochow University, No.92 Zhongnan Street, SIP, 215003, Suzhou, China;School of Basic Medicine and Biological Sciences, Soochow University, 215003, Suzhou, China;

关键词: CEBPG;    EIF4EBP1;    Acute myeloid leukemia;    Proliferation;    Apoptosis;   

DOI  :  10.1186/s12935-021-02305-z

来源: Springer

【 摘 要 】

BackgroundAcute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (CEBPG), a gene implicated in myeloid differentiation and AML progression.MethodsshRNA mediated gene interference was used to down-regulate the expression of CEBPG in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of CEBPG were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of CEBPG was Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), a known repressor of translation. Knockdown of EIF4EBP1 was used to assess its potential role in AML progression downstream of CEBPG.ResultsWe explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found CEBPG was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found CEBPG was overexpressed in AML. Moreover, we observed that CEBPG promotes AML cell proliferation by activating EIF4EBP1, thus contributing to the progression of AML. These findings indicate that CEBPG could act as a potential therapeutic target for AML patients.ConclusionIn summary, we systematically explored the molecular characteristics of CEBPG in AML and identified CEBPG as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for CEBPG in promoting AML progression.

【 授权许可】

CC BY